The objectives of the proposed research are aimed at determining: (1) the pathway of picornavirus morphogenesis and, in particular, the role of empty capsids, (2) the nature and mechanism of action of a virus-specific assembly factor(s) responsible for facilitating the assembly of 14S precursor particles into empty capsids in vitro, (3) the conditions in vitro for the production of poliovirions by means that mimic the maturation process in vivo, and (4) means to isolate and characterize virus-resistant mammalian cells. The role of empty capsids as well as specific viral proteins in morphogenesis will be established by analyzing the behavior of existing temperature-sensitive poliovirus mutants defective in assembly under non-permissive conditions and the consequences of chemicals which block the synthesis or cleavage of viral precursor polypeptides. Finally, normally susceptible cells will be mutagenized, virus-resistant cells isolated, and the viral functions rendered defective in these cells identified.